To achieve enhanced cancer therapy, a sequentially dynamic polymeric drug delivery system (ortho ester-linked PEGylated poly(disulfide)s-based micelle-doxorubicin (PS-g-OEMPEG-DOX)) is successfully constructed. The PEGylated micelle can keep stable in sodium dodecyl sulfate (SDS) solution at pH 7.4, but be prone to DePEGylation and dynamic size changes via the hydrolysis of ortho ester linkages in side chains at tumoral extracellular pH value (6.5). Moreover, the micelle can rapidly release DOX via the cleavage of poly(disulfide)s in backbone at intracellular reductive milieu (10 mmol/L of dithiothreitol (DTT)). The dynamic micelle with detachable PEGylation achieves the stable blood circulation, improved cellular uptake and cytotoxicity, stronger in vitro penetration and inhibition of tumoral multicellular spheroids, and significant in vivo tumor accumulation and inhibition while decreasing side effects. Thus, the sequentially dynamic polymeric micelle with detachable PEGylation can be considered as a promising and effective drug delivery system in cancer therapy.

为了实现增强的癌症治疗，成功构建了顺序动态聚合物药物递送系统（原酸酯连接的聚乙二醇化聚二硫化物基胶束阿霉素（PS- g -OEMPEG-DOX））。聚乙二醇化胶束在 pH 7.4 的十二烷基硫酸钠 (SDS) 溶液中可以保持稳定，但在肿瘤细胞外 pH 值 (6.5) 下，容易通过侧链中的原酸酯键的水解而发生去聚乙二醇化和动态尺寸变化。此外，胶束可以在细胞内还原环境（10 mmol/L的二硫苏糖醇（DTT））下通过主链中的聚（二硫）裂解快速释放DOX。可分离聚乙二醇化的动态胶束实现了血液循环的稳定，提高了细胞的摄取和细胞毒性，对肿瘤多细胞球体具有更强的体外渗透和抑制作用，在体内显着地抑制肿瘤积聚和抑制，同时减少了副作用。因此，具有可分离聚乙二醇化的顺序动态聚合物胶束可以被认为是癌症治疗中一种有前景且有效的药物递送系统。